DOCSLIB.ORG

ERN1 Knockdown Modifies the Impact of Glucose and Glutamine Deprivations on the Expression of EDN1 and Its Receptors in Glioma Cells

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
ERN1 Knockdown Modifies the Impact of Glucose and Glutamine Deprivations on the Expression of EDN1 and Its Receptors in Glioma Cells This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/ licenses/ by-nc-nd/4.0), which permits copy and redistribute the material in any medium or format, provided the original work is properly cited. 72 ENDOCRINE REGULATIONS, Vol. 55, No. 2, 72–82, 2021 doi:10.2478/enr-2021-0009 ERN1 knockdown modifies the impact of glucose and glutamine deprivations on the expression of EDN1 and its receptors in glioma cells Dmytro O. Minchenko1,2, Olena O. Khita1, Dariia O. Tsymbal1, Yuliia M. Viletska1, Myroslava Y. Sliusar1, Yuliia V. Yefimova1, Liudmyla O. Levadna2, Dariia A. Krasnytska1, Oleksandr H. Minchenko1 1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine; 2National Bogomolets Medical University, Kyiv, Ukraine E-mail: [email protected] Objective. The aim of the present investigation was to study the impact of glucose and gluta- mine deprivations on the expression of genes encoding EDN1 (endothelin-1), its cognate receptors (EDNRA and EDNRB), and ECE1 (endothelin converting enzyme 1) in U87 glioma cells in re- sponse to knockdown of ERN1 (endoplasmic reticulum to nucleus signaling 1), a major signaling pathway of endoplasmic reticulum stress, for evaluation of their possible implication in the control of glioma growth through ERN1 and nutrient limitations. Methods. The expression level of EDN1, its receptors and converting enzyme 1 in control U87 glioma cells and cells with knockdown of ERN1 treated by glucose or glutamine deprivation by quantitative polymerase chain reaction was studied. Results. We showed that the expression level of EDN1 and ECE1 genes was significantly up- regulated in control U87 glioma cells exposure under glucose deprivation condition in compari- son with the glioma cells, growing in regular glucose containing medium. We also observed up- regulation of ECE1 gene expression in U87 glioma cells exposure under glutamine deprivation as well as down-regulation of the expression of EDN1 and EDNRA mRNA, being more significant for EDN1. Furthermore, the knockdown of ERN1 signaling enzyme function significantly modified the response of most studied gene expressions to glucose and glutamine deprivation conditions. Thus, the ERN1 knockdown led to a strong suppression of EDN1 gene expression under glucose deprivation, but did not change the effect of glutamine deprivation on its expression. At the same time, the knockdown of ERN1 signaling introduced the sensitivity of EDNRB gene to both glucose and glutamine deprivations as well as completely removed the impact of glucose deprivation on the expression of ECE1 gene. Conclusions. The results of this study demonstrated that the expression of endothelin-1, its receptors, and ECE1 genes is preferentially sensitive to glucose and glutamine deprivations in gene specific manner and that knockdown of ERN1 significantly modified the expression of EDN1, EDNRB, and ECE1 genes in U87 glioma cells. It is possible that the observed changes in the expres- sion of studied genes under nutrient deprivation may contribute to the suppressive effect of ERN1 knockdown on glioma cell proliferation and invasiveness. Key words: ERN1 knockdown, mRNA expression, EDN1, EDNRA, EDNRB, ECE1, glucose and glutamine deprivations, U87 glioma cells Corresponding author: Oleksandr H. Minchenko, Prof, Department of Molecular Biology, Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Leontovycha 9, Kyiv 01030, Ukraine; e-mail: [email protected]. Minchenko, et al. 73 The unfolded protein response is a highly tial for this purpose (Huber et al. 2013; Parzych et al. conserved protein quality control mechanism, acti- 2019). Glucose as well as glutamine are important vated in response to endoplasmic reticulum stress. substrates for glycolysis and glutaminolysis, which The growing tumor requires the endoplasmic retic- are important to glioma development and a more ulum stress for own neovascularization and growth aggressive behavior through regulation of the cell as well as for inhibition of apoptosis under stressful cycle at distinct stages (Colombo et al. 2011). environmental conditions (Drogat et al. 2007; Auf It is interesting to note that endoplasmic reticulum et al. 2010; Doultsinos et al. 2017). The endoplasmic stress and glucose as well as glutamine level are very reticulum stress signaling represents an integrated important and complementary factors for tumor signal transduction pathway that transmits infor- growth and that ERN1 mediated stress signaling can mation about the protein folding status at the endo- significantly modify the effects of glutamine and plasmic reticulum to the nucleus and cytosol to glucose deprivations as well as hypoxia on numerous restore proteostasis (Bravo et al. 2013; Chevet et al. gene expressions (Minchenko et al. 2014, 2016, 2017; 2015; Lhomond et al. 2018; Marciniak 2019). Malig- 2019; Zhao et al. 2017; Tsymbal et al. 2020). However, nant tumors use the unfolded protein response the detailed molecular mechanisms of the interaction and its signaling pathways to augment cancer cells of hypoxia and glucose deprivation with ERN1 medi- proliferation (Dejeans et al. 2015; Manie et al. 2014; ated stress signaling pathway are complex yet and Papaioannou et al. 2018). It is interesting to note that warrant further study. stimulation of ERN1/IRE1 (endoplasmic reticulum The peptide hormone endothelin-1 (EDN1; to nucleus signaling 1/inositol requiring enzyme 1) ET-1) and its related receptors, such as EDNRA and division of the endoplasmic reticulum stress response EDNRB, play an important role not only in the main- is tightly linked to apoptosis and cell death, and inhi- tenance of vascular tone, but they are also localized bition of its functional activity has been demon- to non-vascular structures including epithelial cells, strated to result in substantial anti-proliferative effect glia and neurons and play multiple, complex roles in glioma growth (Auf et al. 2010, 2013; Johnson et al. (Dashwood and Loesch 2009; Khimji and Rockey 2011; Minchenko et al. 2014, 2015c; Markouli et al. 2010; Stow et al. 2011). Endothelin-1 and its recep- 2020). Additionally, suppression of ERN1 endoribo- tors also have co-mitogenic activity, potentiating the nuclease has more robust anti-proliferative influence effects of other growth factors such as PDGF and have on glioma cells and preferentially different impact on been linked to variable diseases including diabetes, the expression of some ERN1-related pathway genes traumatic shock, and tumorigenesis (Minchenko et (Auf et al. 2013; Minchenko et al. 2015c). al. 1999, 2003; Dashwood and Loesch 2009; Khimji Glioblastoma multiforme is the most common and Rockey 2010; Stow et al. 2011; Palmer et al. 2012; and malignant type of primary brain tumor of the Cook et al. 2015; Dojo Soeandy et al. 2019). There are central nervous system with poor prognosis and high also data indicating that EDN1 is a neuropeptide, mortality. The current clinical treatments for glioblas- which is implicated in a number of neural circuits toma consist of tumor resection, radiotherapy, and where its transmitter affects range from a role in chemotherapy (Nayak and Reardon 2017; Almanza et pain and temperature control to its action on the al. 2019; Yang et al. 2020). The rapid growth of cancers hypothalamo-neurosecretory system (Dashwood generates microenvironmental changes in regards to and Loesch 2009). Recently, it was shown that mRNA nutrient deprivation, thus inducing the activation of levels encoding EDN1 and its receptors, known to be endoplasmic reticulum stress signaling pathways, elevated in amyotrophic lateral sclerosis, were sharply cell proliferation, and survival (Obacz et al. 2017; increased by knockdown of C9 (C9ORF72) gene, Zhao et al. 2017; Obiedat et al. 2019; Liu et al. 2020). which encodes a protein that functions in control Furthermore, a better knowledge of tumor responses of endothelin and glutamate signaling (Fomin et al. to nutrient deprivation is required to elaborate better 2018). Differential and tissue-specific production of therapeutical strategies of cell sensibilization, based EDN1 must be tightly regulated in order to preserve on the blockade of survival mechanisms (Iurlaro et these biologically diverse actions. al. 2017; Riabovol et al. 2019; Teramoto and Katoh It is interesting to note that the palmitic acid 2019; Minchenko et al. 2020a, b; Ratushna 2020). increases ET-1 expression in endothelial cells through Cell proliferation and apoptosis are strongly depen- the induction of endoplasmic reticulum stress and dent on glycolysis and glucose level, because there is the activation of protein kinase C, providing a novel the molecular connection between metabolism, cell mechanistic insight into the pathogenesis of obesity- cycle progression, and the delivery of nutrients essen- associated hypertension and cardiovascular diseases 74 ERN1 knockdown modifies the impact of nutrient deficits on EDN1 family genes including atherosclerosis (Zhang et al 2018). The hypoxia responsible. Its promoter and intron regions primary mechanism thought the control of EDN1 contain the HIF binding sites (Khamaisi et al. 2015). bioavailability is the rate of transcription from It has also been shown that endothelin-1 produc- the EDN1 gene. Studies conducted on a variety of tion is controlled by TIMAP-protein phosphatase cell types have identified key transcription factors 1-complex via ECE1 dephosphorylation (Boratko
Load more

Recommended publications
  • Ire1β Negatively Regulates Ire1α Signaling in Response to Endoplasmic Reticulum Stress
    bioRxiv preprint doi: https://doi.org/10.1101/586305; this version posted March 23, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. IRE1 negatively regulates IRE1 signaling in response to endoplasmic reticulum stress Michael J. Grey1,2,3†, Eva Cloots4,5†, Mariska S. Simpson1,6†, Nicole LeDuc1, Yevgeniy V. Serebrenik7, Heidi De Luca1, Delphine De Sutter4, Phi Luong1, Jay R. Thiagarajah1,2,3, Adrienne W. Paton8, James C. Paton8, Markus A. Seeliger9, Sven Eyckerman4, Sophie Janssens5, and Wayne I. Lencer1,2,3* 1Division of Gastroenterology, Hepatology, and Nutrition, Boston Children’s Hospital, Boston, MA 02115 2Harvard Medical School, Boston MA 02115 3Harvard Digestive Disease Center, Boston MA 02115 4VIB-UGent Center for Medical Biotechnology and Department of Biomolecular Medicine, Ghent University, Ghent, Belgium 5Laboratory for ER stress and Inflammation, VIB-UGent Center for Inflammation Research and Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium 6Molecular and Cellular Sciences, Graduate School of Life Sciences, Utrecht University, Utrecht, The Netherlands 7Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511 8Research Centre for Infectious Diseases, Department of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA, Australia 9Department of Pharmacological Sciences, Stony Brook University Medical School, Stony Brook, NY 17794 †These authors contributed equally to this work. 1 bioRxiv preprint doi: https://doi.org/10.1101/586305; this version posted March 23, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder.
    [Show full text]
  • A Human Genome-Wide Rnai Screen Reveals Diverse Modulators That Mediate Ire1a–XBP1 Activation Zhifen Yang1, Jing Zhang1, Dadi Jiang2, Purvesh Khatri3, David E
    Published OnlineFirst February 9, 2018; DOI: 10.1158/1541-7786.MCR-17-0307 Molecular Cancer Research A Human Genome-Wide RNAi Screen Reveals Diverse Modulators that Mediate IRE1a–XBP1 Activation Zhifen Yang1, Jing Zhang1, Dadi Jiang2, Purvesh Khatri3, David E. Solow-Cordero4, Diego A.S. Toesca1, Constantinos Koumenis5, Nicholas C. Denko6, Amato J. Giaccia1, Quynh-Thu Le1, and Albert C. Koong2 Abstract Activation of the unfolded protein response (UPR) signaling pathways is linked to multiple human diseases, including cancer. The inositol-requiring kinase 1a (IRE1a)–X-box binding protein 1 (XBP1) pathway is the most evo- lutionarily conserved of the three major signaling branches of the UPR. Here, we performed a genome-wide siRNA screen to obtain a systematic assessment of genes integrated in the IRE1a– XBP1 axis. We monitored the expression of an XBP1-luciferase chimeric protein in which lucifer- ase was fused in-frame with the spliced (active) form of XBP1. Using cellsexpressingthis reporter construct, we identified 162 genes for which siRNA inhibition re- sulted in alteration in XBP1 splic- ing. These genes express diverse types of proteins modulating a wide range of cellular processes. Pathway analysis identified a set of genes implicated in the pathogenesis of breast cancer. Several genes, including BCL10, GCLM,andIGF1R, correlated with worse relapse-free survival (RFS) in an analysis of patients with triple-negative breast cancer (TNBC). However, in this cohort of 1,908 patients, only high GCLM expression correlated with worse RFS in both TNBC and non-TNBC patients. Altogether, our study revealed unidentified roles of novel pathwaysregulating the UPR, and these findings may serve as a paradigm for exploring novel therapeutic opportunities based on modulating the UPR.
    [Show full text]
  • Ire1α Regulates Macrophage Polarization, PD-L1 Expression And
    bioRxiv preprint doi: https://doi.org/10.1101/2020.02.17.952457; this version posted February 17, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. PLOS Biology 1 IRE1a regulates macrophage polarization, PD-L1 expression and tumor survival 2 By 3 Alyssa Batista1*, Jeffrey J. Rodvold1*, Su Xian2, Stephen Searles1, Alyssa Lew1, Takao 4 Iwawaki3, Gonzalo Almanza1, T. Cameron Waller2, Jonathan Lin4, Kristen Jepsen5, Hannah 5 Carter2, and Maurizio Zanetti1 6 7 1 The Laboratory of Immunology 8 Department of Medicine and Moores Cancer Center 9 University of California, San Diego 10 9500 Gilman Drive 11 La Jolla, CA 92093-081 12 13 14 2Division of Medical Genetics; Department of Medicine, 15 And Bioinformatics and Systems Biology Program 16 University of California San Diego 17 La Jolla, CA 92093 18 19 3Laboratory for Cell Recovery Mechanisms 20 Brain Science Institute 21 RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 22 Japan. 23 24 4Department of Pathology 25 Stanford University 26 300 Pasteur Drive 27 Palo Alto, CA 94305 28 29 5IGM Genomics Center 30 University of California, San Diego 31 9500 Gilman Drive 32 La Jolla, CA 92093-0612. 33 34 35 * These authors contributed equally 36 37 Corresponding author: Maurizio Zanetti 38 39 Ph: (858) 822-5412 40 FAX: (858) 822-5421 41 Email: [email protected] 42 43 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.02.17.952457; this version posted February 17, 2020.
    [Show full text]
  • Endoplasmic Reticulum Stress and the Protein Degradation System in Ophthalmic Diseases
    Endoplasmic reticulum stress and the protein degradation system in ophthalmic diseases Jing-Yao Song1, Xue-Guang Wang2, Zi-Yuan Zhang1, Lin Che1, Bin Fan1 and Guang-Yu Li1 1 Department of Ophthalmology, Second Hospital of Jilin University, ChangChun, China 2 Department of Traumatic Orthopedics, Third People's Hospital of Jinan, Jinan, China ABSTRACT Objective. Endoplasmic reticulum (ER) stress is involved in the pathogenesis of various ophthalmic diseases, and ER stress-mediated degradation systems play an important role in maintaining ER homeostasis during ER stress. The purpose of this review is to explore the potential relationship between them and to find their equilibrium sites. Design. This review illustrates the important role of reasonable regulation of the protein degradation system in ER stress-mediated ophthalmic diseases. There were 128 articles chosen for review in this study, and the keywords used for article research are ER stress, autophagy, UPS, ophthalmic disease, and ocular. Data sources. The data are from Web of Science, PubMed, with no language restrictions from inception until 2019 Jul. Results. The ubiquitin proteasome system (UPS) and autophagy are important degradation systems in ER stress. They can restore ER homeostasis, but if ER stress cannot be relieved in time, cell death may occur. However, they are not independent of each other, and the relationship between them is complementary. Therefore, we propose that ER stability can be achieved by adjusting the balance between them. Conclusion. The degradation system of ER stress, UPS and autophagy are interrelated. Because an imbalance between the UPS and autophagy can cause cell death, regulating that balance may suppress ER stress and protect cells against pathological stress damage.
    [Show full text]
  • Viral Mediated Tethering to SEL1L Facilitates ER-Associated Degradation of IRE1
    bioRxiv preprint doi: https://doi.org/10.1101/2020.10.07.330779; this version posted October 9, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 1 2 3 Viral mediated tethering to SEL1L facilitates ER-associated degradation of IRE1 4 5 6 Florian Hinte, Jendrik Müller, and Wolfram Brune* 7 8 Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany 9 10 * corresponding author. [email protected] 11 12 Running head: MCMV M50 promotes ER-associated degradation of IRE1 13 14 15 Word count 16 Abstract: 249 17 Text: 3275 (w/o references) 18 Figures: 7 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.10.07.330779; this version posted October 9, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 19 Abstract 20 The unfolded protein response (UPR) and endoplasmic reticulum (ER)-associated 21 degradation (ERAD) are two essential components of the quality control system for proteins 22 in the secretory pathway. When unfolded proteins accumulate in the ER, UPR sensors such 23 as IRE1 induce the expression of ERAD genes, thereby increasing protein export from the ER 24 to the cytosol and subsequent degradation by the proteasome. Conversely, IRE1 itself is an 25 ERAD substrate, indicating that the UPR and ERAD regulate each other.
    [Show full text]
  • IRE1 (ERN1) Rabbit Polyclonal Antibody – TA336287 | Origene
    OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for TA336287 IRE1 (ERN1) Rabbit Polyclonal Antibody Product data: Product Type: Primary Antibodies Applications: IF, WB Recommended Dilution: WB: 1:1000-1:2000, IF: 1:100 - 1:250 Reactivity: Human, Mouse, Rat (Does not react with: Primate) Host: Rabbit Clonality: Polyclonal Immunogen: A synthetic peptide within the human IRE1 alpha protein (within residues 700-800). [Swiss- Prot #O75460] Formulation: Tris-glycine, 150 mM NaCl, 0.05% Sodium Azide. Store at -20C. Avoid freeze-thaw cycles. Concentration: lot specific Purification: Immunogen affinity purified Conjugation: Unconjugated Storage: Store at -20°C as received. Stability: Stable for 12 months from date of receipt. Predicted Protein Size: 110 kDa Gene Name: endoplasmic reticulum to nucleus signaling 1 Database Link: NP_001424 Entrez Gene 78943 MouseEntrez Gene 498013 RatEntrez Gene 2081 Human O75460 This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2021 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 3 IRE1 (ERN1) Rabbit Polyclonal Antibody – TA336287 Background: Unfolded protein response (UPR) signaling, mechanism used by eukaryotic cells to cope ER stress, is initiated by three ER-localized protein sensors: PERK (PKR-like ER kinase), ATF (activating transcription factor 6), and IRE1 alpha (inositol-requiring enzyme 1 alpha). UPR- responsive genes's transcriptional activation is regulated by ATF6 and IRE1-XBP1 pathways, and UPR serves three important functions: inhibition of protein translation to restore normal cell functions; activation of signaling to increase production of molecular chaperones involved in protein folding; and activation of signaling that leads to targeting of misfolded proteins in ER for ubiquitination and subsequent degradation; or when ER-stress is not relieved, UPR leads to apoptosis.
    [Show full text]
  • Hypoxic Regulation of EDN1, EDNRA, EDNRB, and ECE1 Gene Expressions in ERN1 Knockdown U87 Glioma Cells
    This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/ licenses/ by-nc-nd/3.0), which permits copy and redistribute the material in any medium or format, provided the original work is properly cited. 250 ENDOCRINE REGULATIONS, Vol. 53, No. 4, 250–262, 2019 doi:10.2478/enr-2019-0025 Hypoxic regulation of EDN1, EDNRA, EDNRB, and ECE1 gene expressions in ERN1 knockdown U87 glioma cells Dmytro O. Minchenko1,2, Daria O. Tsymbal1, Olena O. Riabovol1, Yuliia M. Viletska1, Yuliia O. Lahanovska1, Myroslava Y. Sliusar1, Borys H. Bezrodnyi2, Oleksandr H. Minchenko1 1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine; 2National Bohomolets Medical University, Kyiv, Ukraine E-mail: [email protected] Objective. The aim of the present investigation was to study the effect of hypoxia on the expres- sion of genes encoding endothelin-1 (EDN1) and its cognate receptors (EDNRA and EDNRB) as well as endothelin converting enzyme 1 (ECE1) in U87 glioma cells in response to inhibition of en- doplasmic reticulum stress signaling mediated by ERN1/IRE1 (endoplasmic reticulum to nucleus signaling 1) for evaluation of their possible significance in the control of glioma growth through ERN1 and hypoxia. Methods. The expression level of EDN1, EDNRA, EDNRB, and ECE1 genes as well as micro- RNA miR-19, miR-96, and miR-206 was studied in control and ERN1 knockdown U87 glioma cells under hypoxia by quantitative polymerase chain reaction. Results. It was shown that the expression level of EDN1, EDNRA, EDNRB, and ECE1 genes was up-regulated in ERN1 knockdown glioma cells in comparison with the control glioma cells, be- ing more significant for endothelin-1.
    [Show full text]
  • ERN1 Knockdown Modifies the Effect of Glucose Deprivation on Homeobox Gene Expressions in U87 Glioma Cells
    This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/ licenses/ by-nc-nd/3.0), which permits copy and redistribute the material in any medium or format, provided the original work is properly cited. 196 ENDOCRINE REGULATIONS, Vol. 54, No. 3, 196–206, 2020 doi:10.2478/enr-2020-0022 ERN1 knockdown modifies the effect of glucose deprivation on homeobox gene expressions in U87 glioma cells Dariia O. Tsymbal1, Dmytro O. Minchenko1,2, Olena O. Khita1, Olha V. Rudnytska1, Yulia M. Viletska1, Yulia O. Lahanovska1, Qiuxia He3, Kechun Liu3, Oleksandr H. Minchenko1 1Department of Molecular Biology, Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine; 2Department of Pediatrics, National Bohomolets Medical University, Kyiv, Ukraine; 3Biology Institute Shandong Academy of Sciences, Jinan, China E-mail: [email protected] Objective. The aim of the present investigation was to study the expression of genes encoding homeobox proteins ZEB2 (zinc finger E-box binding homeobox 2), TGIF1 (TGFB induced fac- tor homeobox 1), SPAG4 (sperm associated antigen 4), LHX1 (LIM homeobox 1), LHX2, LHX6, NKX3-1 (NK3 homeobox 1), and PRRX1 (paired related homeobox 1) in U87 glioma cells in response to glucose deprivation in control glioma cells and cells with knockdown of ERN1 (endo- plasmic reticulum to nucleus signaling 1), the major pathway of the endoplasmic reticulum stress signaling, for evaluation of it possible significance in the control of glioma growth through ERN1 signaling and chemoresistance. Methods. The expression level of homeobox family genes was studied in control (transfected by vector) and ERN1 knockdown U87 glioma cells under glucose deprivation condition by real-time quantitative polymerase chain reaction.
    [Show full text]
  • ERN1 and ALPK1 Inhibit Differentiation of Bi-Potential Tumor- Initiating Cells in Human Breast Cancer
    www.impactjournals.com/oncotarget/ Oncotarget, 2016, Vol. 7, (No. 50), pp: 83278-83293 Research Paper ERN1 and ALPK1 inhibit differentiation of bi-potential tumor- initiating cells in human breast cancer Juliane Strietz2,*, Stella S. Stepputtis2,3,*, Bogdan-Tiberius Preca2,3,*, Corinne Vannier2,3, Mihee M. Kim1, David J. Castro1, Qingyan Au1, Melanie Boerries3,5, Hauke Busch3,5, Pedro Aza-Blanc1, Susanne Heynen-Genel1, Peter Bronsert8,9,10, Bernhard Kuster6, Elmar Stickeler7, Thomas Brabletz4, Robert G. Oshima1,#, Jochen Maurer1,2,3,# 1Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA 2Department of Visceral Surgery, University Hospital Freiburg, German Cancer Consortium (DKTK), Freiburg, Germany 3German Cancer Research Center (DKFZ), Heidelberg, Germany 4Department of Experimental Medicine I, University of Erlangen-Nuernberg, Erlangen, Germany 5 Systems Biology of the Cellular Microenvironment at The DKFZ Partner Site Freiburg, German Cancer Consortium (DKTK), Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University Freiburg, Freiburg, Germany 6Technische Universitaet Muenchen, Partner Site of the German Cancer Consortium, Freising, Germany 7Department of OBGYN, University Clinic Aachen (UKA), Aachen, Germany 8Department of Surgical Pathology, University Medical Center Freiburg, Freiburg, Germany 9German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany 10Institute of Pathology, University Medical Center Freiburg, Freiburg, Germany *These authors have contributed equally and share first authorship #These authors have contributed equally and share last authorship Correspondence to: Jochen Maurer, email: [email protected] Robert G. Oshima, email: [email protected] Keywords:ALPK1, ERN1, differentiation therapy, human bi-potential tumor-initiating cells, kinase knockdown Received: March 21, 2016 Accepted: October 21, 2016 Published: November 04, 2016 ABSTRACT Cancers are heterogeneous by nature.
    [Show full text]
  • Detection of H3k4me3 Identifies Neurohiv Signatures, Genomic
    viruses Article Detection of H3K4me3 Identifies NeuroHIV Signatures, Genomic Effects of Methamphetamine and Addiction Pathways in Postmortem HIV+ Brain Specimens that Are Not Amenable to Transcriptome Analysis Liana Basova 1, Alexander Lindsey 1, Anne Marie McGovern 1, Ronald J. Ellis 2 and Maria Cecilia Garibaldi Marcondes 1,* 1 San Diego Biomedical Research Institute, San Diego, CA 92121, USA; [email protected] (L.B.); [email protected] (A.L.); [email protected] (A.M.M.) 2 Departments of Neurosciences and Psychiatry, University of California San Diego, San Diego, CA 92103, USA; [email protected] * Correspondence: [email protected] Abstract: Human postmortem specimens are extremely valuable resources for investigating trans- lational hypotheses. Tissue repositories collect clinically assessed specimens from people with and without HIV, including age, viral load, treatments, substance use patterns and cognitive functions. One challenge is the limited number of specimens suitable for transcriptional studies, mainly due to poor RNA quality resulting from long postmortem intervals. We hypothesized that epigenomic Citation: Basova, L.; Lindsey, A.; signatures would be more stable than RNA for assessing global changes associated with outcomes McGovern, A.M.; Ellis, R.J.; of interest. We found that H3K27Ac or RNA Polymerase (Pol) were not consistently detected by Marcondes, M.C.G. Detection of H3K4me3 Identifies NeuroHIV Chromatin Immunoprecipitation (ChIP), while the enhancer H3K4me3 histone modification was Signatures, Genomic Effects of abundant and stable up to the 72 h postmortem. We tested our ability to use H3K4me3 in human Methamphetamine and Addiction prefrontal cortex from HIV+ individuals meeting criteria for methamphetamine use disorder or not Pathways in Postmortem HIV+ Brain (Meth +/−) which exhibited poor RNA quality and were not suitable for transcriptional profiling.
    [Show full text]
  • Role of Endoplasmic Reticulum Stress Sensor Ire1α in Cellular Physiology, Calcium, ROS Signaling, and Metaflammation
    cells Review Role of Endoplasmic Reticulum Stress Sensor IRE1α in Cellular Physiology, Calcium, ROS Signaling, and Metaflammation Thoufiqul Alam Riaz 1 , Raghu Patil Junjappa 1 , Mallikarjun Handigund 2 , Jannatul Ferdous 3, Hyung-Ryong Kim 4,* and Han-Jung Chae 1,* 1 Department of Pharmacology, School of Medicine, Institute of New Drug Development, Jeonbuk National University, Jeonju 54907, Korea; toufi[email protected] (T.A.R.); [email protected] (R.P.J.) 2 Department of Laboratory Medicine, Jeonbuk National University, Medical School, Jeonju 54907, Korea; [email protected] 3 Department of Radiology and Research Institute of Clinical Medicine of Jeonbuk National University, Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54907, Korea; [email protected] 4 College of Dentistry, Dankook University, Cheonan 31116, Korea * Correspondence: [email protected] (H.-R.K); [email protected] (H.-J.C) Received: 9 April 2020; Accepted: 6 May 2020; Published: 8 May 2020 Abstract: Inositol-requiring transmembrane kinase endoribonuclease-1α (IRE1α) is the most prominent and evolutionarily conserved unfolded protein response (UPR) signal transducer during endoplasmic reticulum functional upset (ER stress). A IRE1α signal pathway arbitrates yin and yang of cellular fate in objectionable conditions. It plays several roles in fundamental cellular physiology as well as in several pathological conditions such as diabetes, obesity, inflammation, cancer, neurodegeneration, and in many other diseases. Thus, further understanding of its molecular structure and mechanism of action during different cell insults helps in designing and developing better therapeutic strategies for the above-mentioned chronic diseases. In this review, recent insights into structure and mechanism of activation of IRE1α along with its complex regulating network were discussed in relation to their basic cellular physiological function.
    [Show full text]
  • Table S1. 103 Ferroptosis-Related Genes Retrieved from the Genecards
    Table S1. 103 ferroptosis-related genes retrieved from the GeneCards. Gene Symbol Description Category GPX4 Glutathione Peroxidase 4 Protein Coding AIFM2 Apoptosis Inducing Factor Mitochondria Associated 2 Protein Coding TP53 Tumor Protein P53 Protein Coding ACSL4 Acyl-CoA Synthetase Long Chain Family Member 4 Protein Coding SLC7A11 Solute Carrier Family 7 Member 11 Protein Coding VDAC2 Voltage Dependent Anion Channel 2 Protein Coding VDAC3 Voltage Dependent Anion Channel 3 Protein Coding ATG5 Autophagy Related 5 Protein Coding ATG7 Autophagy Related 7 Protein Coding NCOA4 Nuclear Receptor Coactivator 4 Protein Coding HMOX1 Heme Oxygenase 1 Protein Coding SLC3A2 Solute Carrier Family 3 Member 2 Protein Coding ALOX15 Arachidonate 15-Lipoxygenase Protein Coding BECN1 Beclin 1 Protein Coding PRKAA1 Protein Kinase AMP-Activated Catalytic Subunit Alpha 1 Protein Coding SAT1 Spermidine/Spermine N1-Acetyltransferase 1 Protein Coding NF2 Neurofibromin 2 Protein Coding YAP1 Yes1 Associated Transcriptional Regulator Protein Coding FTH1 Ferritin Heavy Chain 1 Protein Coding TF Transferrin Protein Coding TFRC Transferrin Receptor Protein Coding FTL Ferritin Light Chain Protein Coding CYBB Cytochrome B-245 Beta Chain Protein Coding GSS Glutathione Synthetase Protein Coding CP Ceruloplasmin Protein Coding PRNP Prion Protein Protein Coding SLC11A2 Solute Carrier Family 11 Member 2 Protein Coding SLC40A1 Solute Carrier Family 40 Member 1 Protein Coding STEAP3 STEAP3 Metalloreductase Protein Coding ACSL1 Acyl-CoA Synthetase Long Chain Family Member 1 Protein
    [Show full text]